One of the richest in acetylcholine (ACh) and choline acetyltransferase (EC.2.3.1.6 ChAc) regions of the brain is corpus striatum. High concentrations, of dopamine and comparatively low of serotonin and norepinephrine classify striatum as a cholinergic and dopaminergic center. Some of the central effects of morphine, such as immobility with catatonic traits could result from the imbalance in transmitters known to occur after administration of morphine. Changes in ACh levels and ChAc activity were found to occur soon after injection of morphine, while significant fluctuations in dopamine and tyrosine hydroxylase activity appeared much later. To explore further the interplay between the central cholinergic and dopaminergic pathways under the influence of narcotic drugs we propose to examine the nerve-terminals of several regions of the rat brain in naive and morphine treated animals. The subcellular distribution of the transmitters and enzymes involved in their synthesis will be explored. Identification of the cholinergic synaptosomes will be achieved by establishing the presence of ChAc residing in the presynaptic membranes. Specific uptake systems of putative transmitters or their precursors will be used to localize the cholinergic or dopaminergic nerve terminals changes in the permeability of the synaptosomal membranes under the influence of narcotic drugs will be studied using the specific uptake of choline and dopamine. All those parameters will be studied in the brains of tolerant, abstinent and control rats. The undersigned agrees to accept responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as the result of this application.